Coagulation factor VIII is a complex of blood proteins that is involved in the initial stage of blood coagulation. Factor VIII exists in a very small amount in normal plasma circulation as a high-molecular weight glycoprotein. This complex is made of a coagulation promoting component (factor VIIIC) that does not exist in patients with hemophilia A, and factor VIII related von Willebrand's protein (factor VIIIR: vWp) that is associated with platelet aggregation and adhesiveness. The latter proteinaceous component undergoes quantitative or qualitative changes in the plasma of patients with von Willebrand's disease. The complex of these two components is believed to be bound to lipoproteins which impart additional stability to the complex in vivo. It is also believed that calcium ions present in optimal concentrations impart additional stability to factor VIIIC.
Hemorrhagic diseases such as hemophilia A and von Willebrand's disease can most effectively be treated by supplementation of factor VIIIC or von Willebrand's factor. This is accomplished by intravenous injection of fresh plasma or a "cryoprecipitate" (a cold plasma precipitate) if the disease is moderate and by administration of an AHF concentrate if the disease is serious.
A cold plasma precipitate is usually prepared by the method described in Pool et al. Nature 203:312 (1964). According to this method, plasma is frozen and slowly thawed at 4.degree. C. to obtain a cold plasma precipitate or cryoprecipitate that is readily re-dissolvable at 37.degree. C. The majority of factor VIII present in the plasma can be recovered in this cryoprecipitate which therefore is a convenient source of supply of a concentrated form of factor VIII that can be used for therapeutic purposes.
Attempts at treating hemophilia A or von Willebrand's disease with fresh whole blood or plasma or a cryoprecipitate have serious disadvantages. For instance, the low concentrations of AHF necessitate administering fairly large quantities of solution to patients by intravenous injection. Therefore, transfusion must be carried out by instillation or intravenous drip. Another problem is that the fibrinogens present in large amounts will sometimes cause undesired side-effects during transfusion (see Yoshioka et al., Rinshio Ketsueki (Clinical Blood), 17: 788 (1976)). The use of an AHF concentrate has the advantage that a comparatively small amount (about 10-40 ml) of solution is sufficient to provide the patient with the required amount of factor VIII. However, a problem still exists in that factor VIII, which is present in plasma in a very small amount, is highly labile and inevitably suffers activity loss during the separation and purification procedures. Since the AHF concentrate requires a fairly large number of steps for its preparation, the recovery of factor VIII from the starting plasma is too low to realize efficient utilization of the precious starting material. The percentage recovery from the starting plasma is generally about from 40 to 60% for the cryoprecipitate and from 10 to 40% for the AHF concentrate (see Baugh et al., Biochemica Biophysica Acta, 371:360 (1974), and Olsen et al., J. Lab. Clin. Med., 89:1278 (1977)).